There is increasing evidence that the most common disorder of hypoglycemia in early infancy, congenital hyperinsulinism, has a genetic basis/bases. In collaboration with investigators from Jerusalem and St. Louis, we have shown that the gene for an autosomal recessive form of hyperinsulinism is located at 11p15.1. We have also demonstrated a founder effect in a group of families of Ashkenazi background. We have also identified an autosomal dominant varient of hyperinsulinism that is clinically less severe and is not linked to the 11p15.1 region. Further studies are needed to identify other genetic defects which cause congenital hyperinsulinism and to define the specific pathophysiology of these defects in B-cell regulation.